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Mitochondrial calcium uptake and targeted therapeutics

Principal Investigator:
  • George Robertson, Dalhousie University
  • Heart and Stroke Foundation

Project Overview

Stroke is the sudden death of brain cells caused by insufficient blood supply to the brain. Parts of the brain that enable us to walk and talk are often damaged most by a stroke. As a result, patients that survive a stroke frequently need assistance from others to take care of themselves. In these ways, stroke not only devastates the survivors but also places a considerable burden on their family and friends as well as the health care system. Development of treatments that reduce brain cell death and disability after a stroke is therefore a major unmet medical need. Flavonoids are a large group of natural chemicals that give fruits their bright colours and protect them from damage by strong sunlight. These compounds have attracted considerable interest as drugs for the treatment of stroke for several reasons. First, it is well known that eating fruits such as apples that contain high amounts of flavonoids reduces the risk of having a stroke. Second, these compounds are safe even when ingested in large amounts. Third, many laboratories have shown that flavonoids found in apples prevent brain cell death in various experimental models for stroke. In previous studies, Dr. Robertson and his team have made a flavonoid-enriched extract from the peel of apples called AF4. Mice that received AF4 for three days were completely resistant to brain damage produced by an experimental stroke. Their most recent studies suggest that the two most common flavonoids in AF4, epicatechin and quercetin, are responsible for the profoundly protective effects of this extract. They are now researching if primary flavonoid components of AF4 (epicatechin andquercetin) can reduce an experimental stroke For this particular project, Dr. Robertson and his team are trying to determine whether these compounds protect the brain by improving the function of a very important part of the cell called the mitochondrion.